This application is in response to RFA-09-09-003 and addresses broad Challenge Area (15) Translational Science and specific Challenge Topic, 15-OD(ORDR)-101: Pilot Projects for Prevention, Early Detection, and Treatment of Rare Diseases. The congenital long QT syndrome (LQTS) is a genetic disorder characterized by a prolonged QT interval on the electrocardiogram (ECG) and life-threatening arrhythmias. The Jervell and Lange-Nielsen syndrome (JLNS) is the most severe form of LQTS, with a hallmark feature of congenital sensorineural hearing loss (SNHL). JLNS patients become symptomatic very early and are at risk for sudden cardiac death if untreated. Sudden cardiac death of infants with undiagnosed JLNS is often reported as sudden infant death syndrome (SIDS). While mass screening of the general population for JLNS is not practical, the prevalence of JLNS in older children with congenital SNHL has been reported as high as 4%. Most infants with SNHL are now identified early by the state newborn hearing screening programs, therefore, creates an opportunity for early detection and treatment of JLNS. We propose an innovative approach to early JLNS diagnosis by cardiac screening of infants with severe-to-profound SNHL identified by the newborn hearing screening program. The goals of this study are to determine the prevalence of JLNS in infants with severe-to-profound SNHL and to evaluate the effectiveness of early JLNS diagnosis. We propose a population-based study of infants with SNHL identified through the California Newborn Hearing Screening Program. Subjects will be recruited for a "prospective cohort" (SNHL diagnosed during the project period) and a "retrospective cohort" (SNHL diagnosed in preceding 4 years). An estimated 1,256 infants and young children with severe-to-profound SNHL will participate in this 2-year study. Cardiac screening will consist of detailed personal and family histories, and a 12-lead ECG. Subjects who are considered high risk will have genetic testing for JLNS mutations. From the prospective cohort, we will calculate the prevalence rate of JLNS among young infants with severe-to-profound SNHL and compared with the reported rates in older children. The impact of early JLNS diagnosis on clinical management will be assessed by the number of infants who receive therapy [[unreadable]-blockers and/or an implantable cardioverter-defibrillator (ICD)] as a result of early diagnosis. The effectiveness of cardiac screening will be evaluated by comparing the retrospective cohort and the prospective cohort to determine the number of cardiac deaths and SIDS that could have been prevented had the cardiac screening been conducted early in the retrospective cohort. Public Health Relevance: The Jervell and Lange-Nielsen syndrome (JLNS) is the most severe form of the congenital long QT syndrome with a hallmark feature of sensorineural hearing loss. Patients with JLNS become symptomatic early in life and are at risk for sudden cardiac death if they are not diagnosed early and properly treated. We propose an innovative approach to early diagnosis of JLNS by cardiac screening of all infants who are identified with sensorineural hearing loss by the California Newborn Hearing Screening Program.